Aspirin might have antioxidant properties and plays an important role in inflammation. Promising evidence from the in vitro fertilization (IVF) literature suggests that low-dose aspirin may improve fecundity, possibly due to improved perfusion early in pregnancy. We conducted a meta-analysis of randomized IVF clinical trials that suggested that aspirin during early gestation may reduce the risk of preterm birth and small-for-gestational-age babies. The EAGeR study is a multi-site, double-blinded randomized trial designed to assess the effects of low-dose aspirin on implantation and pregnancy outcome. It is the largest such study to-date, enrolling 1,228 (535 in the low-dose aspirin group and 543 in the placebo group) women experiencing a recent pregnancy loss who are planning subsequent pregnancies. Each woman was randomly assigned to the treatment group with 81 mg aspirin plus 0.4 mg folic acid daily or the placebo group with 0.4 mg folic acid only. Treatment/placebo administration started prior to conception and continued during pregnancy. Fertility monitors were used to assist with timing of intercourse, home digital pregnancy testing kits were used to determine pregnancy, and daily urine samples were collected to monitor very early pregnancy and pregnancy loss. Pregnancy loss, pregnancy complications and perinatal outcomes were monitored throughout pregnancy. We hypothesized that low-dose aspirin may reduce oxidative stress and inflammation and, therefore, reduce vascular resistance and improve blood flow and placental perfusion. An increased supply of oxygen and nutrients should promote placental and fetal growth, enhance conception rates, reduce pregnancy loss and pregnancy complications and, thereby, improve perinatal outcomes. Using intent to treat analysis, 309 (58%) women in the low-dose aspirin group had livebirths, compared with 286 (53%) in the placebo group (p=00984; absolute difference in livebirth rate 509% 95% CI &#8722;084 to 1102). Pregnancy loss occurred in 68 (13%) women in the low-dose aspirin group, compared with 65 (12%) women in the placebo group (p=07812). In the original stratum, 151 (62%) of 242 women in the low-dose aspirin group had livebirths, compared with 133 (53%) of 250 in the placebo group (p=00446; absolute difference in livebirth rate 920% 051 to 1789). In the expanded stratum, 158 (54%) of 293 women in the low-dose aspirin group and 153 (52%) of 293 in the placebo group had livebirths (p=07406; absolute difference in livebirth rate 171% &#8722;637 to 979). Major adverse events were similar between treatment groups. Low-dose aspirin was associated with increased vaginal bleeding, but this adverse event was not associated with pregnancy loss. Interpretation Preconception-initiated low-dose aspirin was not significantly associated with livebirth or pregnancy loss in women with one to two previous losses. However, higher livebirth rates were seen in women with a single documented loss at less than 20 weeks gestation during the previous year. Low-dose aspirin is not recommended for the prevention of pregnancy loss. Findings from this trial will have important implications not only for women trying to conceive but also for women who want to maintain a healthy pregnancy and achieve optimal perinatal outcomes.